Roche’s multiple sclerosis win puts more pressure on Sanofi

Liver toxicity is a class effect of BTK inhibitors, according to Sanofi, whose tolebrutinib is the lead multiple sclerosis project with this pharmacology. However, Roche’s fenebrutinib and Novartis’s remibrutinib have so far avoided this issue. Today Roche reported topline phase 2 data on its candidate, saying fenebrutinib significantly reduced the number of new gadolinium-enhancing T1 brain lesions versus placebo. Safety will be closely watched when full results are presented, but Roche said this was consistent with previous trials, with no new concerns. And Sanofi still sees a future for tolebrutinib, which remains on partial clinical hold in the US. During a first-quarter call its chief medical officer, Dietmar Berger, said the group was working on a risk-mitigation strategy, and noted that it had not seen further liver tox since close monitoring was introduced. “If the efficacy data is what we hope the monitoring is really not a barrier to uptake,” chief exec Paul Hudson added. Phase 3 could read out by year end. The fourth quarter should also see data on Merck KGaA’s rival evobrutinib, which also went on partial FDA hold in April. Results should shed light on whether the benefits indeed outweigh the risks.

BTK inhibitors in development for multiple sclerosis
Project Company Note
Phase 3
Tolebrutinib Sanofi (ex Principia) On partial US clinical hold; Gemini-1 & 2 trials in RMS fully enrolled, data due late 2023/early 2024; Hercules SPMS fully enrolled; Perseus in PPMS recruiting OUS
Evobrutinib Merck KGaA On US partial clinical hold; EvolutionRMS 1 & EvolutionRMS 2 in RMS fully enrolled, data due Q4 2023
Fenebrutinib (RG7845) Roche Positive data from ph2 Fenopta May 2023; ph3 Fenhance & Fenhance-2 in RMS complete Oct 2025; Fentrepid in PPMS completes Jan 2026
Remibrutinib (LOU064) Novartis Two ph3 studies in RMS (NCT05147220 & NCT05156281) complete Apr 2026
Phase 2
Orelabrutinib (ICP-022) Innocare Ph2 in RMS completes Feb 2026; Biogen pulled out of deal Feb 2023
BIIB091 Biogen   Ph2 in RMS not yet recruiting
Phase 1
IMG-004 Inmagene Biopharmaceuticals Ph1 healthy volunteer data Apr 2023
RMS=relapsing MS; PPMS=primary progressive MS; SPMS=secondary progressive MS. Source: Evaluate Pharma &

Share This Article